rs1363753

Variant names:

• chr19-36997579-G-A
• rs1363753
• ENST00000444991.6:c.1888G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-36997579-G-A
• chr19-36997579-G-C
• chr19-36997579-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000444991.6(ZNF568):​c.1888G>A​(p.Gly630Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.15
• Publications: 21 publications found

Genes affected

ZNF568 (HGNC:25392): (zinc finger protein 568) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in embryonic placenta morphogenesis and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291239 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060214877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1888G>A	p.Gly630Ser	missense_variant	Exon 10 of 10		NP_001191767.1
ZNF568	NM_001204839.2	c.1696G>A	p.Gly566Ser	missense_variant	Exon 9 of 9		NP_001191768.1
ZNF568	XM_017026772.2	c.1888G>A	p.Gly630Ser	missense_variant	Exon 10 of 10		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291239	ENST00000706165.1	c.1888G>A	p.Gly630Ser	missense_variant	Exon 12 of 12			ENSP00000516244.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 195434 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1422384 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 705442

African (AFR) AF: 0.00 AC: 0 AN: 32724

American (AMR) AF: 0.00 AC: 0 AN: 39498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25604

East Asian (EAS) AF: 0.00 AC: 0 AN: 37568

South Asian (SAS) AF: 0.00 AC: 0 AN: 82946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096298

Other (OTH) AF: 0.00 AC: 0 AN: 59358

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000851 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.21
DANN	Benign	0.87
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-0.94	T
PhyloP100		-5.2
PROVEAN	Benign	0.95	N;.
REVEL	Benign	0.046
Sift	Benign	0.47	T;.
Sift4G	Benign	0.20	T;T
Vest4		0.052
MutPred		0.23		Gain of phosphorylation at G566 (P = 0.0084);.;
MVP		0.099
ClinPred		0.052	T
GERP RS		1.6
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1363753; hg19: chr19-37488481;